Surgical glues based on monomers comprising a phosphate function

Abstract

A composition for use as a surgical adhesive for the adhesion of a material to a biological tissue, for the adhesion of biological tissues to one another, for the adhesion of a glue or of a substance to the surface of a biological tissue, as a surgical sealant, for blocking or plugging orifices created by a thread suture or staple suture or by a tissue resection, for blocking an orifice, an incision or a tear in a biological tissue, as a hemostatic agent for stopping bleeding, as a dressing on a biological tissue for covering and protecting a wound, for reinforcing a biological tissue, for attaching and stabilizing a biological tissue. The compositions include a polymerizable monomer with a phosphate function or a phosphonate function and a methacrylate function.

The invention claimed is: 
     
       1. A composition for use as a surgical adhesive for the adhesion of a material to a non-mineralised biological tissue, for the adhesion of non-mineralised biological tissues to one another, for the adhesion of a glue or a substance to the surface of a non-mineralised biological tissue, as surgical sealant, for blocking or plugging orifices created by a thread suture or staple or by a tissue resection, for blocking an orifice, an incision or a tear in a non-mineralised biological tissue, as a haemostatic for stopping bleeding, as a dressing on a non-mineralised biological tissue for covering and protecting a wound, for reinforcing a non-mineralised biological tissue, or for fixing and stabilising a non-mineralised biological tissue, wherein said composition comprises between 10 and 60% by mass relative to the total mass of the composition of a polymerisable monomer comprising a phosphate function or a phosphonate function and a methacrylate function;
 wherein the composition comprises a polymerisable monomer of formula I: 
 
       
         
           
           
               
               
           
         
       
       wherein: 
       R2 is H or CH3; 
       R1, R1′, and R1″ are independently of one another a linear polyether radical, a linear or branched aliphatic radical with C1-C50, an aromatic radical of C6-C18, for which the carbon chain of said radicals can be interrupted by O, S, OCONH and/or can comprise one or more alcohol functions; 
       R1′ is H if c=0; 
       R1″ is H if a=0; 
       b is 1; and 
       a or c is 1 or 0. 
     
     
       2. The composition according to  claim 1 , wherein a=0, R2=H or CH 3  and R′1 and R1 is a linear aliphatic chain of C1-C12. 
     
     
       3. The composition according to  claim 2 , wherein a=0, c=0, R2=CH3 and R1 is a linear aliphatic chain of C1-C12. 
     
     
       4. The composition according to  claim 1 , wherein the polymerisable monomer of formula I is 10-MDP (C 14 H 27 O 6 P) or MEP(C 12 H 19 O 8 P). 
     
     
       5. The composition according to  claim 1 , further comprising between 4% and 30%, by mass in relation to the total mass of the composition, of a first cross-linking agent. 
     
     
       6. The composition according to  claim 4 , further comprising between 30% and 90%, by mass in relation to the total mass of the composition, of a second cross-linking agent. 
     
     
       7. The composition according to  claim 1 , further comprising a co-monomer. 
     
     
       8. The composition according to  claim 7 , wherein said comonomer is selected from the group comprising polybutadiene diacrylates and mono or di-functional monomers such as tert-butyl acrylate, n-butyl acrylate, lauryl acrylate, lauryl methacrylate, methyl acrylate, stearyl methacrylate, hydroxyethyl acrylate, hydroxyethyl methacrylate, acrylic acid, methacrylic acid, 2-ethoxyethyl methacrylate, 2-ethylhexyl acrylate monomer, 2-ethylhexyl methacrylate, 2-phenyloxyethyl methacrylate, 1-(acryloyloxy)-3-(methacryloyloxy)-2-propanol, di(ethylene glycol) ethyl ether acrylate, ethyl acrylate, ethylene glycol methyl ether acrylate, ethylene glycol phenyl ether acrylate, methyl acrylate, 3-(trimethoxysilyl)propyl methacrylate, methyl methacrylate, poly(ethylene glycol) methyl ether acrylate (Mn of 200 to 10000 g/mol), triethylene glycol dimethacrylate, tert-butyl methacrylate, triethylene glycol monoethylether methacrylate, 3-(tris(trimethylsilyloxy)silyl)propyl methacrylate. 
     
     
       9. The composition according to  claim 8 , wherein said co-monomer has a concentration between 1 and 50% by mass in relation to the total mass of the composition. 
     
     
       10. The composition according to  claim 1 , further comprising a photoinitiator. 
     
     
       11. The composition according to  claim 9 , wherein said photoinitiator is selected from the group consisting of bisacylphosphine oxide, Bis(.eta.5-2,4-cylcopentadien-1-yl)-bis(2,6-difluoro-3-(1H-pyrrol-1-yl)-phenyl) titanium, I′ 1-[4-(2-Hydroxyethoxy)-phenyl]-2-hydroxy-2-methyl-1-propane-1-one, 2,4,6-trimethylbenzoyl-phenylphosphinate oxide, 2,4,6-trimethylbenzoyldiphenylphosphine oxide, 2,2-dimethoxyphenyl-2-acetophenone, camphorquinone or 4,4′-bis(diethylamino)benzophenone, the latter associated with N-Phenylglycine, Ethyl-4-(dimethylamino)benzoate, N-Diisopropylethylamine and 4-(Dimethylamino)benzonitrile. 
     
     
       12. The composition according to  claim 9 , wherein said photoinitiator is in a concentration between 0.2 and 10% by mass. 
     
     
       13. The composition according to  claim 4 , wherein the composition comprises between 0.1 and 5% by mass photoinitiator, between 30 and 90% by mass of a second cross-linking agent, between 10 and 50% by mass of polymerisable monomer comprising a phosphate function and a methacrylate function and between 1 and 50% by mass of co-monomer. 
     
     
       14. A non-invasive method for the adhesion of a material to a non-mineralised biological tissue, for the adhesion of non-mineralised biological tissues to one another, for the adhesion of a glue or a substance to the surface of a non-mineralised biological tissue, surgical sealing, for blocking or plugging orifices created by a thread suture or staple or by a tissue resection, for blocking an orifice, an incision or a tear in a non-mineralised biological tissue, for stopping bleeding, for covering and protecting a wound, for reinforcing a non-mineralised biological tissue or for fixing and stabilising a non-mineralised biological tissue, said non-invasive method comprising the steps:
 (i) coating the tissue to be treated with a composition according to  claim 1 , 
 (ii) letting the composition penetrate into said tissue, 
 (iii) inducing the polymerisation of said composition.